Although in vivo studies have indicated a direct stimulatory effect of androgens on hematopoietic stem cells and early erythroblast descendants of these cells, there is virtually no information on the molecular events that underlie specific interactions of these erythropoietic tissues. The proposed project is a study of such events in the anemia of bleeding in normal and mutant mice. A low capacity, high affinity protein receptor for 17 beta-OH estradiol, but not testosterone, has been identified in the cytoplasm of such spleens as well as reticulocyte, but not erythrocyte, lysates. The projected study will undertake the purification of this estradiol receptor and its role in transport to intranuclear structures. The molecular specificity of the steroid ligands in binding will be determined in order to select one or more steroids for the predominance of its erythropoietic effect as opposed to virilization, etc. This would be helpful in the management of refractory anemias.